Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice

Respir Res. 2010 Mar 20;11(1):33. doi: 10.1186/1465-9921-11-33.


Background: Histone deacetylase (HDAC) inhibitors, developed as promising anti-tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines.

Objective: To investigate the protective effect of butyrate, a HDAC inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.

Methods: ALI was induced in Balb/c mice by intratracheally instillation of LPS (1 mg/kg). Before 1 hour of LPS administration, the mice received butyrate (10 mg/kg) orally. The animals in each group were sacrificed at different time point after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid (BALF) and concentrations of nitric oxide (NO) and myeloperoxidase (MPO) activity in lung tissue homogenates were measured by enzyme-linked immunosorbent assay (ELISA). Expression of nuclear factor (NF)-kappaB p65 in cytoplasm and nucleus was determined by Western blot analysis respectively.

Results: Pretreatment with butyrate led to significant attenuation of LPS induced evident lung histopathological changes, alveolar hemorrhage, and neutrophils infiltration with evidence of reduced MPO activity. The lung wet/dry weight ratios, as an index of lung edema, were reduced by butyrate administration. Butyrate also repressed the production of TNF-alpha, IL-1beta and NO. Furthermore, the expression of NF-kappaB p65 in nucleus was markedly suppressed by butyrate pretreatment.

Conclusions: Butyrate had a protective effect on LPS-induced ALI, which may be related to its effect on suppression of inflammatory cytokines production and NF-kappaB activation.

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / prevention & control*
  • Administration, Oral
  • Animals
  • Butyrates / administration & dosage*
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Histone Deacetylase Inhibitors / administration & dosage*
  • Humans
  • Lipopolysaccharides*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Treatment Outcome


  • Butyrates
  • Cytokines
  • Histone Deacetylase Inhibitors
  • Lipopolysaccharides